There have been a number of reports documenting electrochemical (EC) aspects of electrospray ionization mass spectrometry (ESI). For example, the EC process inherent in the normal operation of an electrospray (ES) ion source is well documented. (See, e.g., Van Berkel, G. J., The Electrolytic Nature of Electrospray, Chap. II. In Electrospray Ionization Mass Spectrometry; Cole, R. B. Ed.; Wiley: New York, 1997, pp 65-105; Kebarle, P. & Ho, Y., “The Electrolytic Nature of Electrospray, Chap. I. In Electrospray Ionization Mass Spectrometry; Cole, R. B., Ed.; Wiley: New York, 1997, pp 3-63; Li, Y., et al., Anal. Chem. 2003, 75, 6987-6994; and X. Van Berkel, G. J., Kertesz, Anal. Chem. 2007, 5511-5520, the disclosures of which are each incorporated herein by reference.) To summarize, it has long been known that a metal electrospray capillary, operating at high voltage, can function as an electrode where electrochemical one-electron transfer reactions can occur. Moreover, under specific conditions, and with specific compounds, these electrochemical reactions can be a significant part of the ES spectrum, but under normal operating conditions the EC process does not result in significant ion intensity. (See, e.g., De la Mora, J. F., et al., J. Mass Spectrom. 2000, 35, 939-952; Williams, D. & Young, M. K. Rapid Commun. Mass Spectrom. 2000, 14, 2083-2091; and Williams, D., et al., Rapid Commun. Mass Spectrom. 2000, 15, 182-186, the disclosures of which are incorporated herein by reference.) An example of the experimental conditions required to obtain meaningful EC results with an ES ion source are reported by Van Berkel et al., where first cis-diols were derivatized with ferrocene boronic acid and then the subsequently formed electrochemically active derivative was eluted into the ES ion source with a solvent system containing 100 μM lithium trifluoromethane sulfonate. (See, Van Berkel, G. J., et al., Rapid Commun. Mass Spectrom. 2000, 14, 849-858, the disclosure of which is incorporated herein by reference.) In this example, the role of the lithium trifluoromethane sulfonate is to negate ion suppression effects observed with EC under ES conditions.
Other approaches to amplify the electrochemically generated ion signal, and to gain more control over the EC process, involve hardware modifications to the basic ES design. (See, e.g., Kertesz, V. & Van Berkel, G. J., J. Am. Soc. Mass Spectrom. 2006, 17, 953-961; and Karst, U., Angew. Chem. Int. Ed. 2004, 43, 2476-2478, the disclosures of which are incorporated herein by reference.) For example, Van Berkel incorporates a porous flow-through electrode to extend the capabilities of the EC inherent in the ES process. (See, Van Berkel, G. J., et al., Anal. Chem. 2005, 77, 8041-8049, the disclosure of which is incorporated herein by reference.) Another approach to enhancing EC capabilities to ES has been to add an EC cell in-line, upstream of the ES ion source. For example, Seiwart and Karst have recently reported an application of such an in-line EC/ESI-RP-HPLC-MS. (Seiwert, B. & Karst, U., Anal. Bioanal. Chem. 2007, 17 Apr. Epub, the disclosure of which is incorporated herein by reference.) The advantage of such an in-line EC cell is that the electrochemical process can be better controlled. The disadvantage of the in-line EC cell technique is the requirement of additional complicated hardware, it is sensitive, but it can often produce unwanted reactions.
The result is that despite the research conducted on EC/ESI by researchers over the years there are no real practical applications of this phenomenon. The reason for the slow pace of development results from the shortcomings discussed above, namely, the requirement in conventional systems of a separate, unique ion source to affect ECI, and a lack of sensitivity in these conventional ESI ion sources. In fact, so poor have the results been that there has not been a single direct study of the actual sensitivity of EC/ESI MS. Finally, underlying both of the above limitations is that current EC/ESI technology lacks an effective means to remove electrons and keep them removed from the eluting sample medium. Accordingly, an improved EC/ESI methodology is needed to provide a simple, high sensitivity chemical analytical technique